An Immersive Virtual Reality Intervention for Preoperative Anxiety and Distress Among Adults Undergoing Oncological Surgery: Protocol for a 3-Phase Development and Feasibility Trial.

BACKGROUND: Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment. OBJECTIVE: This study seeks to develop and investigate a targeted PSA intervention in patients undergoing oncological surgery using a single preoperative VR exposure. The primary objectives are to (1) develop a novel VR program for patients undergoing oncological surgery with general anesthesia; (2) assess the feasibility, including acceptability, of a single exposure to this intervention; (3) assess the feasibility, including acceptability, of outcome measures of PSA; and (4) use these results to refine the VR content and outcome measures for a larger trial. A secondary objective is to preliminarily assess the clinical utility of the intervention for PSA. METHODS: This study comprises 3 phases. Phase 1 (completed) involved the development of a VR prototype targeting PSA, using multidisciplinary iterative input. Phase 2 (data collection completed) involves examining the feasibility aspects of the VR intervention. This randomized feasibility trial involves assessing the novel VR preoperative intervention compared to a VR control (ie, nature trek) condition and a treatment-as-usual group among patients undergoing breast cancer surgery. Phase 3 will involve refining the prototype based on feasibility findings and input from people with lived experience for a future clinical trial, using focus groups with participants from phase 2. RESULTS: This study was funded in March 2019. Phase 1 was completed in April 2020. Phase 2 data collection was completed in January 2024 and data analysis is ongoing. Focus groups were completed in February 2024. Both the feasibility study and focus groups will contribute to further refinement of the initial VR prototype (phase 3), with the final simulation to be completed by mid-2024. CONCLUSIONS: The findings from this work will contribute to the limited body of research examining feasible and broadly accessible interventions for PSA. Knowledge gained from this research will contribute to the final development of a novel VR intervention to be tested in a large population of patients with cancer before surgery in a randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04544618; https://www.clinicaltrials.gov/study/NCT04544618. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55692.

Tibial osteochondroma with thick cartilage which mimicked a chondrosarcoma: A case report.

We report a case of tibial osteochondroma in a 25-year-old female who presented with a palpable calf mass. This mass was associated with a thick cartilaginous cap on cross-sectional imaging, suggesting chondrosarcoma. A CT-guided biopsy was performed, and histology, however, was consistent with osteochondroma. Orthopedic oncology recommended surgical excision due to the potential high sampling error with chondroid lesions. The patient underwent surgical resection, resulting in a final diagnosis of osteochondroma. No post-surgical complications occurred, and a 12-month follow-up showed no evidence of local recurrence. This case highlights the atypical imaging feature of a thick cartilaginous cap in a benign etiology without malignant transformation.

A Humeral Osteosarcoma Mimicking Osseous Leiomyosarcoma: A Case Report.

Osteosarcoma stands as one of the primary mesenchymal bone neoplasms commonly encountered in clinical practice. This malignancy often presents with a wide range of distinctive imaging characteristics. Here, we present a unique case wherein a delayed diagnosis of high-grade osteosarcoma occurred due to the absence of an osteoid matrix in the initial imaging studies. A 61-year-old female, initially presented with a left humeral fracture. As the healing of the fractured bone was delayed and the possibility of a pathologic fracture was considered, a CT-guided biopsy was performed. Histological examination of the biopsy sample initially suggested an osseous leiomyosarcoma. The lack of osteoid matrix on radiographs including aggressive intra-medullary mass seen on MRI, combined with the patient's age, appeared consistent with a diagnosis of leiomyosarcoma of bone. As a result, the initial diagnosis was not called into question. Due to neurovascular involvement, this led to a forequarter amputation. However, upon microscopic examination of the amputation specimen, certain areas exhibited features indicative of malignant osteoid deposition, ultimately supporting a revised diagnosis of high-grade osteosarcoma. This case underscores the critical importance of considering the limitations of core biopsy samples, especially when dealing with suspected limb masses associated with pathological fractures. Radiographs and CT scans can prove invaluable in ruling out subtle adjacent osteoid, and ultimately a multidisciplinary approach to the diagnosis of osteosarcoma is imperative to ensure accurate identification.

Diphenylphosphinylhydroxylamine (DPPH) Affords Late-Stage S-imination to access free-NH Sulfilimines and Sulfoximines.

Sulfilimines, as potential aza-isosteres of sulfoxides, are valued as building blocks, auxiliaries, ligands, bioconjugation handles, and as precursors to versatile S(VI) scaffolds including sulfoximines and sulfondiimines. Here, we report a thioether imination methodology that exploits O-(diphenylphosphinyl)hydroxyl amine (DPPH). Under mild, metal-free, and biomolecule-compatible conditions, DPPH enables late-stage S-imination on peptides, natural products, and a clinically trialled drug, and shows both excellent chemoselectivity and broad functional group tolerance. This methodological report is extended to an efficient and high-yielding one-pot reaction for accessing free-NH sulfoximines with diverse substrates including ones of potential clinical importance. In the presence of a rhodium catalyst, sulfoxides are S-iminated in higher yields to afford free-NH sulfoximines. S-imination was validated on an oxidatively delicate amatoxin to give sulfilimine and sulfoximine congeners. Interestingly, these new sulfilimine and sulfoximine-amatoxins show cytotoxicity. This method is further extended to create sulfilimine and sulfoximine-Fulvestrant and buthionine analogues.

5-Hydroxypyrroloindoline Affords Tryptathionine and 2,2'-bis-Indole Peptide Staples: Application to Melanotan-II.

With peptides increasingly favored as drugs, natural product motifs, namely the tryptathionine staple, found in amatoxins and phallotoxins, and the 2,2'-bis-indole found in staurosporine represent unexplored staples for unnatural peptide macrocycles. We disclose the efficient condensation of a 5-hydroxypyrroloindoline with either a cysteine-thiol or a tryptophan-indole to form a tryptathionine or 2-2'-bis-indole staple. Judicious use of protecting groups provides for chemoselective stapling using α-MSH, which provides a basis for investigating both chemoselectivity and affinity. Both classes of stapled peptides show nanomolar Ki's, with one showing a sub-nanomolar Ki value.